Treatment A (Reference) Treatment B (Test) Test/Ref
STUDY 1
Parameter 100 mg CANA + 2 X 500 mg MET IR
(n=58)		 2 X (50 mg CANA/500 mg MET) IR FDC
(n=58)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 1507.20 1471.39 97.62 (94.32-101.05)
AUClast 11436.06 11300.29 98.81 (96.07-101.63)
AUC∞ (ng.h/mL)a 11804.70 11648.74 98.68 (95.80-101.64)
tmax(h) 4.00 (0.98 – 6.00)b 4.00 (1.00 – 8.00)c  
t1/2 (h) 4.28 (0.966)b 4.13 (0.719)  
STUDY 2
Parameter 100 mg CANA + 2 X 850 mg MET IR
(n=62)		 2 X (50 mg CANA/850 mg MET) IR FDC
(n=62)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 2181.83 2145.93 98.35 (95.31-101.49)
AUClast 16322.17 16098.88 98.63 (95.85-101.50)
AUC∞ (ng.h/mL) 16775.23 16602.04 98.97 (96.18-101.84)
tmax(h) 4.00 (1.00-6.23)d 4.00 (1.50-6.00)e  
t1/2 (h) 4.54 (0.67)d 4.65 (1.13)e  
STUDY 3
Parameter 100 mg CANA + 2 X 1000 mg MET IR
(n=58)		 2 X (50 mg CANA/1000 mg MET) IR FDC
(n=58)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 2274.31 2141.21 94.15(91.00-97.40)
AUClast 16828.48 15899.55 94.48(91.90-97.13)
AUC∞ (ng.h/mL)f 17327.58 16447.21 94.92(92.14-97.78)
tmax(h) 3.00 (1.00-6.00) 3.98 (1.50-6.00)g  
t1/2 (h) 4.68 (1.09)f 4.79 (1.09)g  
STUDY 4
Parameter 300 mg CANA + 2 X 500 mg MET IR
(n=60)		 2 X (150 mg CANA/500 mg MET) IR FDC
(n=60)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 1195.92 1178.57 98.55 (94.91-102.33)
AUClast 9292.72 9256.26 99.61 (96.17-103.17)
AUC∞ (ng.h/mL) 9615.39 9543.12 99.25 (95.74-102.89)
tmax(h) 4.00 (0.98-6.03)h 4.00 (1.50-7.98)b  
t1/2 (h) 4.64 (1.17)h 4.51 (1.01)b  
STUDY 5
Parameter 300 mg CANA + 2 X 850 mg MET IR
(n=61)		 2 X (150 mg CANA/850 mg MET) IR FDC
(n=61)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 2042.38 1910.31 93.53(90.00-97.20)
AUClast 15013.95 14537.47 96.83(93.92-99.83)
AUC∞ (ng.h/mL)c 15614.58 15184.15 97.24(94.24-100.34)
tmax(h) 3.00 (0.98-6.00)b 4.00 (0.98-6.00)i  
t1/2 (h) 4.67 (1.08)i 4.71 (0.98)  
STUDY 6
Parameter 300 mg CANA + 2 X 1000 mg MET IR
(n=62)		 2 X (150 mg CANA/1000 mg MET IR) FDC
(n=62)		 Estimated Ratio, %
(90% CI)
(Test/Ref.)
Cmax (ng/mL) 2309.04 2099.46 90.92(87.03-94.99)
AUClast 18256.73 16873.75 92.42(89.42-95.54)
AUC∞ (ng.h/mL)j 19026.61 17471.82 91.83(88.82-94.93)
tmax(h) 4.00 (1.00-6.00)e 4.00 (1.00-10.00)e  
t1/2 (h) 5.01 (0.89)d 5.06 (0.90)d  
Note: metformin IR tablets supplied as Glucophage® IR tablets. an=57; bn=63; cn=59; dn=66; en=68; fn=56; gn=60; hn=61; in=62; jn=58; AUClast, area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration; AUC∞, area under the plasma concentration-time curve from time 0 to infinite time; CI: confidence interval; Cmax, maximum observed plasma concentration; n: total number of participants; Ref: reference; t1/2 (h), terminal elimination half-time and represented by arithmetic mean (SD); tmax (h), time to reach the maximum plasma concentration and reported as median (range).
Table 4: Summary statistics for geometric means and ratio of geometric means with corresponding 90% confidence intervals for metformin pharmacokinetic parameters following administration of 2 IR FDC tablets (50 or 100 mg canagliflozin/500, 850, or 1,000 mg metformin) compared to coadministration of individual IR canagliflozin (100 or 300 mg) and 2 metformin (500, 850, and 1,000 mg) tablets at equivalent doses.
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